The present invention relates to novel polypeptides having c-AMP-producing activity, and amides, esters or salts thereof. The present invention further relates to the use thereof.
As a new biologically active peptide derived from the brain hypothalami, the testes or the like, polypeptide PACAP38 consisting of 38 amino acid residues has recently been discovered in humans, sheep and rats. The human-derived, sheep-derived and rat-derived PACAP38 polypeptides which are identical to one another in their amino acid sequence have the following formula: EQU His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr-Ser-Arg-Tyr-Arg-Lys-Gln-Met-Ala-Val -Lys-Lys-Tyr-Leu-Ala-Ala-Val-Leu-Gly-Lys-Arg-Tyr-Lys-Gln-Arg-Val-Lys-Asn-Ly s (SEQ ID NO: 1).
PACAP38 enhances the production of intracellular c-AMP in hypophysis cells and the production of c-AMP of astroglia cells, which, in turn, increases the survival time of nerve cells. The activity of PACAP38 has also been found in PACAP27-a polypeptide consisting of 27 amino acid residues on the N-terminal side of PACAP38 [Biochem. Biophys. Commun., 16.4., 567-574 (1989); European Patent Unexamined Publication No. 404,652]. Further, the same activity as that of PACAP27 has also been confirmed in polypeptides PACAP26, PACAP25, PACAP24 and PACAP23 consisting of 26 to 23 amino acid residues, respectively, on the N-terminal side of PACAP38.
The amino acid situated at the 17-position of PACAP38, i.e., methionine, is liable to be oxidized.